ACE Inhibitors or ARBs Discontinuation in Context of COVID-19 Pandemic (ACORES-2)

ACE Inhibitors or ARBs Discontinuation for Clinical Outcome Risk Reduction in Patients Hospitalized for the Endemic Severe Acute Respiratory Syndrome Coronavirus (SARS-CoV-2) Infection: the Randomized ACORES-2 Study

Since December 2019, a novel coronavirus called SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) has caused an international outbreak of respiratory illness described as COVID-19.

Individuals with a history of cardiovascular disease develop a more severe illness and have higher rates of death.

Because of the potential interaction between RAS blockers and SARS-CoV-2 mechanism of infection, there are ongoing scientific discussions on whether they should be stopped or continued in patients with COVID-19.

It is crucial to determine whether RAS blockers should be discontinued or not in patients with COVID-19.

Study Overview

• Status: Terminated
• Conditions: History of Cardiovascular Disease Treated With RAS Blockers and With SARS-CoV-2 Infection
• Intervention / Treatment: Drug: 1: discontinuation of RAS blocker therapy; Drug: 2: continuation of RAS blocker therapy

• Study Type: Interventional
• Enrollment (Actual): 44
• Phase: Phase 3

Contacts and Locations

Study Locations

• France
  • Paris, France, 75013
    • Cardiologie, Groupe Hospitalier Pitié-Salpêtrière

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Age ≥ 18 years old.
• Chronically treated with RAS blockers (ACE inhibitors or ARBs on the last prescription prior to admission with a treatment duration ≥ 1 month).
• Diagnosis of COVID-19 confirmed by the presence of SARS-CoV-2 on any biological sample with any detection method.
• Patients hospitalized in a non-intensive care unit.
• Pregnancy test at inclusion visit for women of childbearing potential.
• Women of childbearing potential must agree to use adequate contraception according to recommendations related to contraception and pregnancy testing in clinical trials, by Clinical Trial Facilitation Group (CTFG).

Exclusion Criteria:

• Shock requiring vasoactive agents.
• Acute respiratory distress syndrome requiring invasive mechanical ventilation.
• Circulatory assistance.
• History of malignant hypertension according to the definition of the 2018 ESC/ESH guidelines on hypertension.
• Uncontrolled blood pressure despite the use of five antihypertensive drugs.
• History of nephrotic syndrome.
• History of hospitalization for hemorrhagic stroke in the past 3 months.
• RAS blockers therapy previously stopped > 48h.
• No affiliation to the French Health Care System "Sécurité Sociale".
• Inability to obtain informed consent.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 1: discontinuation of RAS blocker therapy; discontinuation of RAS blocker therapy	Drug: 1: discontinuation of RAS blocker therapy; discontinuation of RAS blocker therapy; Other Names: discontinuation of RAS blocker therapy
Active Comparator: 2: continuation of RAS blocker therapy; continuation of RAS blocker therapy	Drug: 2: continuation of RAS blocker therapy; continuation of RAS blocker therapy; Other Names: continuation of RAS blocker therapy

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Time to clinical improvement from day 0 to day 28 (improvement of two points on a seven-category ordinal scale, or live discharge from the hospital, whichever comes first)	Time to clinical improvement from day 0 to day 28 (improvement of two points on a seven-category ordinal scale, or live discharge from the hospital, whichever comes first)	from day 0 to day 28 or hospital discharge

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Primary safety endpoint: major adverse cardiac events defined as the composite of cardiovascular death, myocardial infarction, stroke or acute heart failure at day 28	Major adverse cardiac events defined as the composite of cardiovascular death, myocardial infarction, stroke or acute heart failure at day 28	at day 28
Clinical status as assessed with the seven-category ordinal scale on days 7, 14 and 28.	Clinical status as assessed with the seven-category ordinal scale. The seven-category ordinal scale consisted of the following categories: not hospitalized with resumption of normal activities; not hospitalized, but unable to resume normal activities; hospitalized, not requiring supplemental oxygen; hospitalized, requiring supplemental oxygen; hospitalized, requiring nasal high-flow oxygen therapy, noninvasive mechanical ventilation, or both; hospitalized, requiring ECMO, invasive mechanical ventilation, or both; death.	at days 7, 14 and 28
Number of days alive free of oxygen.	Number of days alive free of oxygen.	from day 0 to day 28 or hospital discharge
Number of days alive outside hospital until day28	Number of days alive outside hospital	at day28
Number of days alive free of intensive-care unit (ICU) admission or mechanical Ventilation (invasive or non-invasive) until day28	Ventilation (invasive or non-invasive)	at day28
Number of days alive free of mechanical ventilation (invasive or non-invasive) until day28	Number of days alive free of mechanical ventilation (invasive or non-invasive)	at day28
Number of days alive free of ICU admission until day28	Number of days alive free of ICU admission	at day28
Rate of all-cause mortality at day 28	Rate of all-cause mortality	at day 28
Rate of cardiovascular death at day 28	Rate of cardiovascular death	at day 28
Number of days alive free of acute kidney injury until hospital discharge	Number of days alive free of acute kidney injury	at day 28 to hospital discharge

Collaborators and Investigators

• Sponsor: Assistance Publique - Hôpitaux de Paris
• Collaborators: Groupe Hospitalier Pitie-Salpetriere
• Investigators: Principal Investigator: Gilles MONTALESCOT, MD, PhD, Institut Cardiologie - Pitié Salpêtrière(APHP) / ACTION Study Group / Univ. Paris 6 (UPMC) - INSERM UMRS 1166

Study record dates

Study Major Dates

• Study Start (Actual): April 9, 2020
• Primary Completion (Actual): December 9, 2020
• Study Completion (Actual): January 9, 2021

Study Registration Dates

• First Submitted: March 28, 2020
• First Submitted That Met QC Criteria: March 28, 2020
• First Posted (Actual): April 1, 2020

Study Record Updates

• Last Update Posted (Actual): April 9, 2021
• Last Update Submitted That Met QC Criteria: April 8, 2021
• Last Verified: April 1, 2021

More Information

Terms related to this study

• Keywords: SARS-CoV-2; Cardiovascular disease; RAS blockers
• Additional Relevant MeSH Terms: Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Virus Diseases; Respiratory Tract Infections; Respiratory Tract Diseases; Pneumonia, Viral; Pneumonia; Lung Diseases; COVID-19; Cardiovascular Diseases; Infections
• Other Study ID Numbers: APHP200409

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No